Enaminones are a class of enamines, i.e., .alpha.,.beta.-unsaturated amines analogous to enols. Enamines are Schiff bases, and are highly unstable in aqueous solutions. As such, enamines are used as potential prodrugs (agents which yield an amine on hydrolysis) providing a lipophilic, but acid-labile, carrier group to the active pharmacophore.
Anticonvulsant enaminones have been developed through previous work [1] by Dr. K. R. Scott and others at Howard University. Based on the success of this work the present inventors have synthesized a homologous series of enaminone esters bearing an isoxazole moiety. The isoxazole ring system was found to be a potent and selective GABA receptor agonist in earlier work of Johnston et al., [2] and Curtis et al. [3] on muscimol, 5. Johnston [4] later found muscimol to possess weak, but specific, GABA uptake inhibitory properties on rat brain slices, while Schosboe et al. [5] found the same property in cultured astrocytes. The anticonvulsant effect of muscimol [6] and the GABA.sub.A receptor agonist THIP (4,5,6,7-tetrahydro-isoxazolo[5,4-c]pyridin-3-ol), 6 [7] both of which exert their specific action on postsynaptic GABA receptors, is also known. ##STR2##
The substitution of the methyl group on the isoxazole ring was also reported as producing a highly potent cholinergic channel activator, 7 [8]. ##STR3##